Interaction between Neuronal Depolarization and MK-801 in SH-SY5Y Cells and the Rat Cortex.
- Author:
Yeni KIM
1
;
Miran SEO
;
Yun Il LEE
;
So Young KIM
;
Eun Ah CHO
;
Se Hyun KIM
;
Yong Min AHN
;
Ung Gu KANG
;
Yong Sik KIM
;
Yong Sung JUHNN
Author Information
- Publication Type:Original Article
- Keywords: AKT; Glycogen synthase kinase 3beta; Extracellular legulated kinase 1/2; KCl; Electro convulsive shock; MK-801
- MeSH: Animals; Dizocilpine Maleate*; Electroconvulsive Therapy; Electroshock; Glycogen Synthase Kinases; Humans; Male; Neurons*; Phosphorylation; Phosphotransferases; Psychotic Disorders; Rats*; Rats, Sprague-Dawley
- From:Psychiatry Investigation 2008;5(2):94-101
- CountryRepublic of Korea
- Language:English
- Abstract: OBJECTIVE: The interaction between MK-801, a model of psychosis and KCl-induced depolarization or electroconvulsive shock (ECS), a therapeutic model of electroconvulsive therapy (ECT), was investigated in SH-SY5Y cells and the rat frontal cortex. METHODS: SH-SY5Y cells were pretreated with 1 microM MK-801 for 15 min, followed by cotreatment with 100 mM KCl for 5 min. MK-801 was reintroduced after the KCl was washed out, and the samples were incubated before harvesting. For the experiments in rats, male Sprague-Dawley rats were treated with MK-801 followed by ECS. Immunoblot analyses of glycogen synthase kinase 3beta (GSK3beta) (Ser9), AKT (Ser473) and extracellular legulated kinase (ERK)1/2 in SH-SY5Y cells and the rat frontal cortex were performed. RESULTS: KCl-induced neuronal depolarization resulted in the transient dephosphorylation of AKT (Ser473) and GSK3beta (Ser9), followed by increased phosphorylation of the enzymes in SH-SY5Y cells. Cotreatment with MK-801 and KCl inhibited the initial dephosphorylation of AKT and GSK3beta produced by KCl-induced neuronal depolarization. Similarly, ECS resulted in the transient dephosphorylation of AKT (Ser473) and GSK3beta (Ser9), whereas cotreatment with MK-801 inhibited the initial dephosphorylation of AKT (Ser473) and GSK3beta (Ser9) produced by ECS in the rat frontal cortex. No significant interaction was observed between MK-801 and KCl in the dephosphorylation of ERK1/2. CONCLUSION: These results suggest that an antagonistic interplay between MK-801 and neuronal depolarization by KCl or ECS is involved the regulation of AKT (Ser473) and GSK3beta (Ser9) phosphorylation.
